LUTETIUM (177LU) VIPIVOTIDE TETRAXETAN for De novo metastatic hormone-sensitive prostate cancer (mHSPC)

Inclusion criteria

• {"criterion_text":"- Signed a written informed consent form prior to any trial specific procedures Note: In case of physical incapacitation, a trusted representative of their choice, which is not the Investigator or sponsor, can sign on the behalf of the patients."}
• {"criterion_text":"- Stable or declining PSA level but not a rising one"}
• {"criterion_text":"- Serum PSA of ≥ 0.2 ng/mL at 6 to 8 months after ADT initiation"}
• {"criterion_text":"- Testosterone level < 50 ng/dl or < 1.7 nmol/L"}
• {"criterion_text":"- Be fit enough for 177Lu-PSMA-617 treatment: • Adequate bone marrow function: hemoglobin ≥ 90 g/L (in absence of red blood cell transfusion within 4 weeks prior to randomization), absolute neutrophil count ≥ 1.5 x109/L, platelet count >100 x109/L • Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.0 x upper limit of normal (ULN), or ≤ 5.0 x ULN in the presence of liver metastases; bilirubin < 1.5 x ULN (unless known or suspected Gilbert syndrome, then < 3 x ULN is permitted) • Adequate renal function: calculated creatinine clearance ≥ 50 ml/min (using the MDRD or CKD EPI method)"}
• {"criterion_text":"- For sexually active men with female partners of reproductive potential or with pregnant women, agreement to use a condom with another effective contraceptive method during trial participation and up to 14 weeks after study treatment completion."}
• {"criterion_text":"- Affiliated to the social security system or in possession of equivalent private health insurance (according to local regulations for participation in clinical trials)."}
• {"criterion_text":"- Willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up."}
• {"criterion_text":"- Aged ≥ 18 years old"}
• {"criterion_text":"- Life expectancy > 6 months as per investigator estimate"}
• {"criterion_text":"- ECOG performance status ≤ 2"}
• {"criterion_text":"- Men with histologically or cytologically confirmed adenocarcinoma of the prostate"}
• {"criterion_text":"- De novo metastatic disease defined by clinical or radiographic evidence of metastases at diagnosis (i.e. before any treatment started). If not available, a more recent imaging can be used"}
• {"criterion_text":"- Measurable disease or bone lesions evaluable according to PCWG3 criteria. Patients with doubtful metastases are not eligible"}
• {"criterion_text":"- A pre-randomization 68Ga-PSMA-11 PET/CT scan performed within 4 weeks prior to randomization in the trial. FDG PET scan is not required for this protocol. All patients will be treated independently from the results of pre-randomization PSMA PET scan: patients with PSMA-positive or PSMA-negative disease according to PROMISE 2.0 criteria (see table below) are eligible."}
• {"criterion_text":"- Have 6 to 8 months of previous AND ongoing standard systemic treatment for prostate cancer at the time of signing the written informed consent form, consisting in either: • ADT with docetaxel* ± radiotherapy ** • ADT with an androgen receptor signaling inhibitor (ARSI) (i.e., abiraterone (plus prednisone), or apalutamide or darolutamide or enzalutamide) ± radiotherapy ** • ADT with docetaxel* plus an ARSI (i.e. abiraterone (plus prednisone), or darolutamide, or enzalutamide) ± radiotherapy** Note: *Docetaxel must have been stopped at least 4 weeks ahead of randomization. ** Previous radiotherapy to the primary tumor and/or to the metastases is accepted as long as it was not PSMA-based and must has been completed at least 4 weeks ahead of randomization."}

Exclusion criteria

• {"criterion_text":"- Any evidence of cancer progression (including a rising PSA level, clinical progression, or radiological progression)"}
• {"criterion_text":"- Ongoing participation in another clinical trial involving an investigational product.. Treatment with any investigational product must have ended within 30 days prior to inclusion in the trial.."}
• {"criterion_text":"- Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons"}
• {"criterion_text":"- Persons deprived of their liberty or under protective custody or guardianship"}
• {"criterion_text":"- Prior or concurrent PSMA-based radioligand therapy or other PSMA target treatments"}
• {"criterion_text":"- Known hypersensitivity to the components of the study therapy or its analogs"}
• {"criterion_text":"- Any condition preventing the use of the standard of care and/or specific experimental treatments tested in the trial"}
• {"criterion_text":"- Any of the following within 6 months before randomization: stroke, myocardial infraction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure New York Heart Association (NYHA) Class III or IV"}
• {"criterion_text":"- Hypertension not controlled by an anti-hypertensive treatment (systolic blood pressure [sBP] ≥ 160 mmHg or diastolic blood pressure [dBP] ≥ 95 mmHg)"}
• {"criterion_text":"- Severe or uncontrolled concurrent disease, infection or co-morbidity"}
• {"criterion_text":"- Pathological findings consistent with small cell carcinoma of the prostate"}
• {"criterion_text":"- History of malignancy within the previous 3 years of inclusion with the exception of successfully treated basal or squamous cell skin carcinoma"}

Primary endpoints

• {"endpoint_text":"- Overall Survival (OS) is defined as the time from the date of randomization to the date of death due to any cause. Patients still alive at time of the analysis will be censored at the date of last news.","definition_or_measurement_approach":"Overall Survival (OS) is defined as the time from the date of randomization to the date of death due to any cause. Patients still alive at time of the analysis will be censored at the date of last news."}
• {"endpoint_text":"- Radiographic Progression-free survival (rPFS) is defined as the time from randomization to the date of radiographic progression according to PCWG3 criteria by investigator assessment, or death, whichever occurs first. In absence of radiographic progression or death, the data will be censored at the date of the last PCWG3 radiographic assessment.","definition_or_measurement_approach":"Radiographic Progression-free survival (rPFS) is defined as the time from randomization to the date of radiographic progression according to PCWG3 criteria by investigator assessment, or death, whichever occurs first. In absence of radiographic progression or death, the data will be censored at the date of the last PCWG3 radiographic assessment."}

Secondary endpoints

• {"endpoint_text":"- Efficacy_Castration-Resistance Prostate Cancer-Free Survival (CRPC-FS) is defined as the time from randomization to the onset of castration-resistant prostate cancer or death from any cause, whichever occurs first. In absence of castration-resistance or death, the data will be censored at the date of the last PCWG3 assessment (minimum date PSA/imaging).","definition_or_measurement_approach":"Time from randomization to onset of castration-resistant prostate cancer or death; censored at last PCWG3 assessment if neither event observed."}
• {"endpoint_text":"- Efficacy_Prostate cancer-specific survival (PCSS) is defined as the time from the date of randomization to the date of death due to prostate cancer. Death due to another cause than prostate cancer will be censored at the date of death. Patients still alive at time of the analysis will be censored at the date of last news.","definition_or_measurement_approach":"Time from randomization to death due to prostate cancer; deaths from other causes censored; survivors censored at date of last news."}
• {"endpoint_text":"- Efficay_PSA response will be assessed by the maximum change of PSA (rise or fall) from baseline over the treatment period. A complete PSA response is defined by an undetectable level of serum PSA.","definition_or_measurement_approach":"Maximum change of PSA from baseline during treatment period; complete response = undetectable serum PSA."}
• {"endpoint_text":"- Efficacy_Skeletal-related event-free survival (SRE-FS) is defined as the time from the randomization date to the date of diagnosis of either an SRE (fracture, or a bone pain requiring radiation therapy, or a spinal cord compression, or a preventive surgery to the bones) or death, whichever occurs first. Events will be evaluated by the investigators. No systematic X-Ray will be performed. In absence of SRE or death, data will be censored at the date of last news.","definition_or_measurement_approach":"Time from randomization to diagnosis of SRE (fracture, bone pain requiring RT, spinal cord compression, preventive bone surgery) or death; investigator-assessed; censored at last news if none."}
• {"endpoint_text":"- Efficacy_Time to severe urinary event (SUE) is defined as the time from the randomization date to the date of diagnosis of either one of the following SUE, whichever occurs first: urinary retention with need for a urinary catheter, suprapubic catheter, double J stent, nephrostomy, treatment of the prostate by radiotherapy or trans-urethral resection of the prostate or prostatectomy done to relieve patients with local symptoms. In absence of SUE, data will be censored at the date of last news.","definition_or_measurement_approach":"Time from randomization to diagnosis of specified severe urinary events (e.g., urinary retention requiring catheter, suprapubic catheter, double J stent, nephrostomy, prostate radiotherapy, TURP, prostatectomy); censored at last news if none."}
• {"endpoint_text":"- Efficacy_Time to initiation of subsequent (first and second) anti-cancer systemic therapy for CRPC is defined as the time from randomization date to the date of initiation of first anti-cancer systemic therapy for CRPC (TTSST1) and time from randomization to initiation of second anti-cancer systemic therapy for CRPC (TTSST2). In absence of initiation, data will be censored at date of last news.","definition_or_measurement_approach":"Time from randomization to initiation of first (TTSST1) and second (TTSST2) subsequent systemic anti-cancer therapy for CRPC; censored at last news if not initiated."}
• {"endpoint_text":"- Efficacy of subsequent (first and second) anti-cancer systemic therapy for CRPC will be assessed by either PSA response or rPFS, or OS and will be defined as the time from first and second anti-cancer systemic therapy for CRPC to disease progression or death from any cause, whichever comes first.","definition_or_measurement_approach":"From initiation of subsequent systemic therapy to disease progression or death; assessed by PSA response or rPFS or OS."}
• {"endpoint_text":"- Efficacy_Quality of Life (QoL) will be evaluated using the Brief Pain Inventory-Short Form (BPI-SF) and the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.","definition_or_measurement_approach":"QoL assessed by BPI-SF and FACT-P questionnaires."}
• {"endpoint_text":"- Safety_Toxicity will be evaluated according to NCI-CTCAE v5.0.","definition_or_measurement_approach":"Adverse events graded per NCI-CTCAE v5.0."}
• {"endpoint_text":"- Exploratory_Biomarkers assessment to identify molecular characteristics and genetic or phenotypic abnormalities to correlate with disease outcome.","definition_or_measurement_approach":"Biomarker analyses to identify molecular/genetic/phenotypic features correlated with outcomes."}
• {"endpoint_text":"- Exploratory_Early PSMA PET evaluation and correlation between PSA and PSMA uptake variation will be assessed at 3 months (after cycle 2) according to PROMISE 2.0 criteria. In case of progression detected at early PSMA PET scan, it would not be considered for stopping treatment.","definition_or_measurement_approach":"Early PSMA PET at 3 months (after cycle 2) per PROMISE 2.0 criteria; progression on early PSMA PET does not mandate stopping treatment."}
• {"endpoint_text":"- Exploratory_Identification of PSMA PET imaging biomarkers to predict response and disease outcome will be assessed at pre-randomization based on semiquantitative analysis and total tumoral volume expressing PSMA.","definition_or_measurement_approach":"Pre-randomization semiquantitative PSMA PET analyses and total tumor PSMA-expressing volume to identify imaging biomarkers."}
• {"endpoint_text":"- Exploratory_Radiation dosimetry of tumor tissues and normal organs (notably in salivary gland, bone marrow and kidney) to predict response and toxicity respectively will be perfomed on post-therapeutic images performed after the first cycle of 177Lu PSMA-617 (at least at 4 hours for output patients or 4 hours and 24 hours and Day 5 in case of hospitalization).","definition_or_measurement_approach":"Post-therapeutic dosimetry after first 177Lu-PSMA-617 cycle (imaging at ~4h outpatient or 4h, 24h and Day 5 if hospitalized) to predict response and toxicity in tumor and normal organs."}

France

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

07-10-2025

Processing Time Days

567

Number Of Participants

300

Belgium

Earliest CTIS Part Ii Submission Date

29-04-2026

Latest Decision Or Authorization Date

08-05-2026

Processing Time Days

9

Number Of Sites

4

Number Of Participants

20

Italy

Earliest CTIS Part Ii Submission Date

30-03-2026

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

31

Number Of Sites

5

Number Of Participants

25

Netherlands

Earliest CTIS Part Ii Submission Date

03-04-2026

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

38

Number Of Sites

4

Number Of Participants

20

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Novartis / AAA (Advanced Accelerator Applications)","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"NOVARTIS EUROPHARM LIMITED","duties_or_roles":"Named in product authorisation information (product holder/associated organisation)","organisation_type":""}